DESCRIPTION (Applicant's Description): The long-term goal of this project is to understand how the vertebrate embryo establishes its antero-posterior and dorso-ventral axes. In the previous grant period we established that the maternal cytoplasmic protein beta catenin plays a pivotal role in this process in the amphibian Xenopus laevis. In the absence of beta catenin, embryos gastrulate and form three germ layers but lack the dorsal derivatives (neural tube, notochord, somites, anterior endoderm) of those germ layers. We found that beta catenin was an essential component of a Xwnt signaling pathway, lying downstream of Xwnt and GSK-3 and upstream of the zygotic transcription factor siamois. This proposal is a continuation of these studies. Specifically, there are four questions that we aim to answer: 1. What is the role of the transcription factor XTcf3 in axis formation? 2. What is the role of Xnr3 in axis formation? 3. Is a head forming pathway downstream of XTcf3/beta catenin? 4. Is Xaxin the essential regulator of beta catenin function in axis formation? In recent years, it has become clear that the mechanisms governing differentiation of the early embryo are conserved across species, and used throughout development and in adult tissues to regulate patterning proliferation and regeneration. One example of this conservation is the Wnt signaling pathway, which is conserved in many of its components from sea urchin to mammals. Several lines of evidence implicate this pathway in cancer. Mutations of beta catenin have been found in a wide variety of tumor types (including cancer of the colon, duodenum, stomach, skin, breast and bladder), indicating a potent role for b-catenin as an oncogene. This study aims to increase our understanding of the regulation of beta catenin (Aim 4), the interactions of beta catenin (Aim 1) and the repertoire of direct target genes (Aim 2 and 4). This understanding is a prerequisite for the design of strategies for therapeutic interference with this pathway in anticancer treatment.